The Clinical Impact of CLIR Tools toward Rapid Resolution of Post-Newborn Screening Confirmatory Testing for X-Linked Adrenoleukodystrophy in California

• Main Authors: Hao Tang (Author), Jamie Matteson (Author), Piero Rinaldo (Author), Silvia Tortorelli (Author), Robert Currier (Author), Stanley Sciortino (Author)
• Format: Book
• Published: MDPI AG, 2020-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Since the start of X-linked adrenoleukodystrophy (ALD) newborn screening in California, more than half of the diagnosed cases were found to have an ATP binding cassette subfamily D member 1 (<i>ABCD1</i>) gene variant of uncertain significance (VUS). To determine retrospectively the likelihood that these were true positive cases, we used a web-based post-analytical tool in Collaborative Laboratory Integrated Reports (CLIR). Confirmatory plasma very long-chain fatty-acids (VLCFA) profiles for ALD screen positive infant boys were run through the CLIR ALD tool. We compared the distribution by <i>ABCD1</i> variant classification (pathogenic, likely pathogenic, VUS, and no variant) with the CLIR tool score interpretation (non-informative, possibly ALD, likely ALD, and very likely ALD) and the current case diagnosis. The study showed that CLIR tool positive interpretations were consistent with 100% of the pathogenic and likely pathogenic variants on the <i>ABCD1</i> gene if a more conservative guideline was used. The tool interpretations were also consistent with screened cases that were determined to not have disease (our no-disorder group). The CLIR tool identified 19 diagnosed ALD cases with VUS to be potential false positives, representing a 40% reduction among all diagnosed ALD cases with VUS. The reduction could be extended to 65% if a more aggressive threshold was used. Identifying such preventable false positives could alleviate the follow-up burden for patients, their families, and California Special Care Centers.

Item Description

10.3390/ijns6030062
2409-515X